1. The Field of the Invention
The present invention relates to a method for the selective methylation of a hydroxy group at the 6-position of erythromycin A derivatives.
2. Description of the Prior Art
6-O-Methylerythromycins are useful as anti-bacterial agents or intermediates for the synthesis of the anti-bacterial agents. For example, 6-O-methylerythromycin A is not only stable in the acidic condition but also has a strong anti-bacterial activity when compared with erythromycin A. Especially, this compound shows an excellent effect for treatment of infections by oral administration, and therefore it is a useful anti-bacterial agent.
However, since erythromycin A has many hydroxy groups as shown by the following formula (I), it is difficult to methylate only a specific hydroxy group at the 6-position selectively. ##STR1##
As the previous method for methylating the hydroxy group at the 6-position of erythromycin A, there is known a method for preparing a 6-O-methylerythromycin A derivative which comprises reacting an erythromycin A derivative, substituted with benzyloxycarbonyl groups at a hydrogen atom of the 2'-hydroxy group and a methyl group of the 3'-dimethylamino group, with a methylating agent in the presence of a base in a polar aprotic solvent in order to methylate the hydroxy group at the 6-position (U.S. Pat. No. 4,331,803). In this method, however, are obtained various kinds of the compounds which are methylated at hydroxy groups at any other than the 6-position together with the 6-O-methyl form, and therefore, this method requires the complicated procedure for purification of the objective 6-O-methyl form, and the yield of the 6-O-methyl form is low.